Prof Giampietro Schiavo
Professor of Cellular Neuroscience
Department of Neuromuscular Diseases
UCL Queen Square Institute of Neurology
- Joined UCL
- 7th Apr 2003
The maintenance of the unique morphology of a neuron, which is based on the strict polarisation into axonal and dendritic compartments, is crucial for its functions and survival. Compartmental identity is ensured by a network of axonal transport pathways allowing efficient communication over long distances. Axonal transport constitutes the backbone of long-distance crosstalk in neurons, functionally connecting peripheral compartments, such as synapses, with events occurring in the soma and vice versa. The research efforts of the Molecular NeuroPathobiology Laboratory are focused on proving the central hypothesis that the impairment of the selectivity and/or the efficiency of long-range communication in neurons caused by defects in vesicular traffic constitutes a major pathogenic mechanism in neurodegenerative disorders.
Our laboratory has played a major role in the field by defining the mechanism responsible for the uptake of neurotrophins, their receptors and virulence factors, such as tetanus toxin, and its coupling with the axonal retrograde transport pathway. Furthermore, we have demonstrated the essential role of cytoplasmic dynein in this process and the functional link between mutations in this molecular motor and pathologies of motor and sensory neurons. Given its expertise in neurobiology, our laboratory has been acting as a driving force for the study of axonal retrograde transport in health and disease. As a consequence, it has become a reference centre for the analysis of this process in animal models of neurodegeneration and through international collaborations for the study of the axonal transport of pathogens and viral vectors, such as poliovirus and adenovirus.
Our major research achievements have been:
1. Elucidation of the machinery regulating endocytosis coupled to axonal retrograde transport. Our work has led to the functional identification of a novel endocytic pathway linked to fast retrograde transport, which is required for the targeting of neurotrophins to the soma and their signalling.
2. The definition of the key role of molecular motors in motor neuron homeostasis. Our findings pinpoint the crucial roles of the dynein motor complex and the homeostasis of axonal traffic in neuronal survival.
3. Unravelling the role of specific lipids and their metabolic products in regulated secretion. Our results highlight novel and specific functions of phosphoinositides and the hydrolysis products of membrane phospholipids in exocytosis and membrane recycling.
Giampietro Schiavo has shown strong commitment to student training by organising a neuroscience course at the Galilean School of Higher Education, University of Padua, and contributes/has contributed to PhD programmes at UCL, Institute Pasteur (F), Cancer Research UK London Research Institute. He regularly acts as primary and secondary supervisor of PhD students at UCL, NIH (USA), ETH (CH), DIBIT/Istituto scientifico San Raffaele (I) and TIGEM (I).
Giampietro Schiavo gained his degree in Chemistry and Pharmaceutical Technology from the University of Padua (Italy) in 1988, followed in 1992 by a PhD in Biological Sciences under the supervision of Prof. Cesare Montecucco at the same University. From the beginning of his scientific training, he demonstrated a keen interest in addressing the importance of bacterial toxins in human pathogenesis. Working in a multidisciplinary team, he learned the foundation of interdisciplinary research and the basis for translating basic discoveries into medical outcomes. During his studies, he performed functional analyses on the interaction of several bacterial toxins, such as diphtheria, pertussis and anthrax toxins, with membranes. His work clarified how these proteins gain access to cells and participate in pathogenesis. These studies contributed to the first recombinant diphtheria vaccine now used worldwide in humans.
However, the main focus of his PhD was the mechanism of action of clostridial neurotoxins. With a series of pioneering experiments, he demonstrated that the inhibition of synaptic activity caused by tetanus and botulinum neurotoxins is due to a specific protease activity. He showed that these neurotoxins cleave three synaptic proteins playing fundamental roles in neurotransmitter release. This discovery was instrumental for the field of SNARE biology and generated great interest worldwide. Sponsored by an EMBO Fellowship, he then moved to the laboratory of Prof. J. Rothman at the Memorial Sloan Kettering Cancer Center in New York. Here he demonstrated, novel interactions between the synaptic calcium sensor synaptotagmin, SNAREs and phosphoinositides.
In 1997, he established his laboratory at the Imperial Cancer Research Fund in London. His high-collaborative research programme, which focuses on the analysis of axonal transport has yielded important results on the role of mutations of motor proteins in neurodegeneration (with Prof. Fisher and Greensmith, UCL), neurotrophin signalling (Prof. Ibanez, Karolinska Institute), the role of specific lipids in neurosecretion (Prof. Montecucco, University of Padua), the central action of botulinum and tetanus neurotoxins (Drs. Caleo and Restani, CNR Pisa) to cite a few.